avacopan   Click here for help

GtoPdb Ligand ID: 9450

Synonyms: CCX-168 | CCX168 | Tavneos®
Approved drug PDB Ligand Immunopharmacology Ligand
avacopan is an approved drug (FDA (2021), EMA (2022))
Compound class: Synthetic organic
Comment: Avacopan is a small molecule, competitive and orally bioactive antagonist of human C5a1 receptor [1]. It was originally proposed as an alternative to steroid (glucocorticoid) therapy for ANCA-associated vasculitis [3,7]. The evidence confirming C5, C5a and the C5a receptor as anti-inflammatory and anti-cancer drug targets was reviewed by Horiuchi and Tsukamoto (2016) [2].
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 5
Hydrogen bond donors 2
Rotatable bonds 9
Topological polar surface area 61.44
Molecular weight 581.27
XLogP 7.52
No. Lipinski's rules broken 1
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Canonical SMILES O=C(C1CCCN(C1c1ccc(cc1)NC1CCCC1)C(=O)c1c(C)cccc1F)Nc1ccc(c(c1)C(F)(F)F)C
Isomeric SMILES O=C([C@H]1CCCN([C@H]1c1ccc(cc1)NC1CCCC1)C(=O)c1c(C)cccc1F)Nc1ccc(c(c1)C(F)(F)F)C
InChI InChI=1S/C33H35F4N3O2/c1-20-12-15-25(19-27(20)33(35,36)37)39-31(41)26-10-6-18-40(32(42)29-21(2)7-5-11-28(29)34)30(26)22-13-16-24(17-14-22)38-23-8-3-4-9-23/h5,7,11-17,19,23,26,30,38H,3-4,6,8-10,18H2,1-2H3,(H,39,41)/t26-,30-/m0/s1
1. Bekker P, Dairaghi D, Seitz L, Leleti M, Wang Y, Ertl L, Baumgart T, Shugarts S, Lohr L, Dang T et al.. (2016)
Characterization of Pharmacologic and Pharmacokinetic Properties of CCX168, a Potent and Selective Orally Administered Complement 5a Receptor Inhibitor, Based on Preclinical Evaluation and Randomized Phase 1 Clinical Study.
PLoS ONE, 11 (10): e0164646. [PMID:27768695]
2. Horiuchi T, Tsukamoto H. (2016)
Complement-targeted therapy: development of C5- and C5a-targeted inhibition.
Inflamm Regen, 36: 11. [PMID:29259684]
3. Jayne D. (2019)
Complement inhibition in ANCA vasculitis.
Nephrol Ther, 15 (6): 409-412. [PMID:31631015]
4. Jayne DRW, Bruchfeld AN, Harper L, Schaier M, Venning MC, Hamilton P, Burst V, Grundmann F, Jadoul M, Szombati I et al.. (2017)
Randomized Trial of C5a Receptor Inhibitor Avacopan in ANCA-Associated Vasculitis.
J Am Soc Nephrol, 28 (9): 2756-2767. [PMID:28400446]
5. Kettritz R. (2017)
Vasculitis: A CLEAR argument for targeting complement in ANCA vasculitis.
Nat Rev Nephrol, 13 (8): 448-450. [PMID:28529340]
6. Merkel PA, Jayne DR, Wang C, Hillson J, Bekker P. (2020)
Evaluation of the Safety and Efficacy of Avacopan, a C5a Receptor Inhibitor, in Patients With Antineutrophil Cytoplasmic Antibody-Associated Vasculitis Treated Concomitantly With Rituximab or Cyclophosphamide/Azathioprine: Protocol for a Randomized, Double-Blind, Active-Controlled, Phase 3 Trial.
JMIR Res Protoc, 9 (4): e16664. [PMID:32088663]
7. Onuora S. (2021)
Avacopan offers alternative to steroids for ANCA-associated vasculitis.
Nat Rev Rheumatol, 17 (5): 249. [PMID:33846585]
8. Osman M, Cohen Tervaert JW, Pagnoux C. (2021)
Avacopan for the treatment of ANCA-associated vasculitis.
Expert Rev Clin Immunol, 17 (7): 717-726. [PMID:34006155]
9. Serling-Boyd N, Wallace ZS. (2021)
Management of primary vasculitides with biologic and novel small molecule medications.
Curr Opin Rheumatol, 33 (1): 8-14. [PMID:33164993]